Radiochemical Synthesis and Evaluation in Non-Human Primates of 3-[C]methoxy-4-aminopyridine: A Novel PET Tracer for Imaging Potassium Channels in the CNS.

Demyelination, the loss of the protecting sheath of neurons, contributes to disability in many neurological diseases. In order to fully understand its role in different diseases and to monitor treatments aiming at reversing this process, it would be valuable to have PET radiotracers that can detect and quantify molecular changes involved in demyelination such as the uncovering and upregulation of the axonal potassium channels K1.1 and K1.2. Carbon-11 labeled radiotracers present the advantage of allowing for multiple scans on the same subject in the same day. Here, we describe [C]3MeO4AP, a novel C-labeled version of the K channel tracer [F]3F4AP, and characterize its imaging properties in two non-human primates including a monkey with a focal brain injury sustained during a surgical procedure 3 years prior to imaging. Our findings show that [C]3MeO4AP is brain permeable, metabolically stable and has high plasma availability. When compared with [F]3F4AP, [C]3MeO4AP shows very high correlation in volumes of distribution (), confirming a common target. [C]3MeO4AP shows slower washout than [F]3F4AP, suggesting stronger binding. Finally, similar to [F]3F4AP, [C]3MeO4AP is highly sensitive to the focal brain injury. All these features make it a promising radioligand for imaging demyelinated lesions.